• antagonist
  • However, in the presence of the adenosine antagonist, 3-isobutyl-1-methylxanthine, 1S,3R-ACPD had no significant effect on basal cAMP, but it inhibited cAMP formation stimulated by the D1 agonist, SKF 38393. (aspetjournals.org)
  • The encoded protein (the A2A receptor) is abundant in basal ganglia, vasculature, T lymphocytes, and platelets and it is a major target of caffeine, which is a competitive antagonist of this protein. (wikipedia.org)
  • Several commonly used opioid drugs including etorphine and buprenorphine have been demonstrated to bind to nociceptin receptors, but this binding is relatively insignificant compared to their activity at other opioid receptors in the acute setting (however the non-analgesic NOPr antagonist SB-612,111 was demonstrated to potentiate the therapeutic benefits of morphine). (wikipedia.org)
  • Antagonists
  • While several A2A receptor antagonists have progressed to clinical trials for the treatment of Parkinson's disease, A2AR blockade in the context of cancer is less characterized. (wikipedia.org)
  • Theophylline and caffeine are nonselective adenosine antagonists that are used to stimulate respiration in premature infants. (wikipedia.org)
  • Antagonists targeting NOP are under investigation for their role as treatments for depression and Parkinson's disease, whereas NOP agonists have been shown to act as powerful, non-addictive painkillers in non-human primates. (wikipedia.org)
  • Recent publications demonstrate that adenosine A3 receptor antagonists (SSR161421) could have therapeutic potential in bronchial asthma (17,18). (wikipedia.org)
  • DP1 gene knockout and/or DP1 inhibition by receptor antagonists markedly reduces airway inflammation, obstruction, hypersensitivity, and pro-allergic cytokine and chemokine production in a mouse model of ovalbumin-induced asthma as well as allergic symptoms in a guinea pig model of allergic conjunctivitis, rhinitis, and asthma. (wikipedia.org)
  • potent
  • PGE2>Prostaglandin F2alpha>PGI2=thromboxane A2, with PGD2 being more than 100-fold more potent than PGE2 in binding to and stimulating DP1. (wikipedia.org)
  • L-644,698, BW 245C, BW A868C, and ZK 110841, have been synthesized, found to be about as potent as PGD2 in binding to and stimulating DP1, and used to study the function of this receptor. (wikipedia.org)
  • NECA
  • A series of new 2-alkynyl and 2-cycloalkynyl derivatives of adenosine-5'-N-ethyluronamid(NECA) and of N-ethyl-l'-deoxy-l'-(6-amino-2-hexynyl-9H-purin-9-yl)-b-D-ribofuranuronamid(1e, HENECA), bearing hydroxy, amino, chloro, and cyano groups in the side chain, were synthesized. (unicam.it)
  • The presence of an a-hydroxyl group in the alkynyl chain of NECA derivatives accounts for the A2 agonist potency, leading to compounds endowed with sub-nanomolar affinity in binding studies. (unicam.it)
  • To test this hypothesis, we examined the effects of pre- and posttreatment of adenosine and 5′- N -ethylcarboxamidoadenosine (NECA), a nonselective stable AR agonist, on LPS-induced lung injury. (physiology.org)
  • Mice were given vehicle or LPS intratracheally followed by adenosine, NECA, or vehicle instilled via the internal jugular vein. (physiology.org)
  • Importantly, posttreatment with adenosine or NECA recovers lung vascular barrier and reduces inflammation induced by LPS challenge. (physiology.org)
  • nitric oxide sy
  • Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. (pubmedcentralcanada.ca)
  • tyrosine kinase re
  • ATP is crucial for ALOX5's metabolic activity A proline-rich region (residues 566-577), sometimes termed a SH3-binding domain, which promotes its binding to proteins with SH3 domains such as Grb2 and may thereby link the enzyme's regulation to tyrosine kinase receptors. (wikipedia.org)
  • myocardial
  • Adenoscan® (adenosine) is an approved pharmacological stress agent indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately. (clinicaltrials.gov)
  • As with the A1, the A2A receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow. (wikipedia.org)
  • The A2A receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. (wikipedia.org)
  • Adenosine is used as an adjunct to thallous (thallium) chloride TI 201 or Tc99m myocardial perfusion scintigraphy (nuclear stress test) in patients unable to undergo adequate stress testing with exercise. (wikipedia.org)
  • mGluR
  • In the absence of adenosine A2 receptor blockade, the mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) stimulated cAMP accumulation through a pertussis toxin-insensitive mechanism that could be blocked by L-serine-o-phosphate, but not by L(+)-2-amino-3-phosphonopropionic acid. (aspetjournals.org)
  • physiological
  • A potential physiological role for the interaction between the D1 and adenosine-dependent stimulatory metabotropic receptor was sought by examining this interaction on striatal GABA release. (aspetjournals.org)
  • However, in altered cardiac function, such as hypoperfusion caused by hypotension, heart attack or cardiac arrest caused by nonperfusing bradycardias, adenosine has a negative effect on physiological functioning by preventing necessary compensatory increases in heart rate and blood pressure that attempt to maintain cerebral perfusion. (wikipedia.org)
  • As these "classical" opioid receptors were identified 30 years earlier in the mid-1960s, the physiological and pharmacological characterization of NOP as well as therapeutic development targeting this receptor remain decades behind. (wikipedia.org)
  • compounds
  • The compounds were studied in binding and functional assays to assess their potency for the A2 compared to A1 adenosine receptor. (unicam.it)
  • Although NOP shares high sequence identity (~60%) with the 'classical' opioid receptors μ-OP (MOP), κ-OP (KOP), and δ-OP (DOP), it possesses little or no affinity for opioid peptides or morphine-like compounds. (wikipedia.org)
  • dopamine
  • The A2A receptor is also expressed in the brain, where it has important roles in the regulation of glutamate and dopamine release, making it a potential therapeutic target for the treatment of conditions such as insomnia, pain, depression, drug addiction and Parkinson's disease. (wikipedia.org)
  • As a result, Adenosine receptor A2A decreases activity in the Dopamine D2 receptors. (wikipedia.org)
  • In 1991, the phenomenon of receptor crosstalk was observed between adenosine A2A (A2A) and dopamine D2 receptor (DRD2) thus suggesting the formation of heteromers. (wikipedia.org)
  • While initially thought to be a receptor heterodimer, a review from 2015 determined that the A2A-DRD2 heteromer is a heterotetramer composed of A2A and DRD2 homodimers (i.e., two adenosine A2A receptors and two dopamine D2 receptors). (wikipedia.org)
  • Regulation
  • In beta N22 cells the IP prostanoid receptor was expressed at similar levels to those in wild-type NG108-15 cells, and treatment with iloprost resulted in a similar down-regulation of cellular Gs alpha levels. (biochemj.org)
  • These results demonstrate that the phenomenon of agonist-induced specific G-protein down-regulation is determined by the levels of expression of the receptor. (biochemj.org)
  • Adenosine also plays a role in regulation of blood flow to various organs through vasodilation. (wikipedia.org)
  • This receptor is involved in the regulation of numerous brain activities, particularly instinctive and emotional behaviors. (wikipedia.org)
  • platelets
  • ADP-dependent aggregation is mediated by two receptors: the purinergic P2Y1, coupled to Gαq, mediates the shape in the structure of platelets and triggers the aggregation process. (wikipedia.org)
  • When it is added to saline-diluted whole blood in the test cuvette, it stimulates the ADP receptors on platelets, activating the platelets. (wikipedia.org)
  • Thrombin receptor activating peptide-6 (TRAP-6) activates platelets through the thrombin receptor protease activated receptor-1 (PAR-1). (wikipedia.org)
  • Binding of TRAP-6 to PAR-1 causes a conformational change in the GPIIb/IIIa receptors on platelets, giving them high affinity for fibrinogen. (wikipedia.org)
  • membrane
  • 300 fmol/mg of membrane protein of the receptor. (biochemj.org)
  • Exposure of beta N22 cells to the beta-adrenergic agonist isoprenaline resulted maximally in some 55% decrease in membrane-associated levels of Gs alpha, without effect on membrane levels of Gi2 alpha, Gi3 alpha, G(o) alpha or Gq alpha/G11 alpha. (biochemj.org)
  • It is the case for the vast majority of responses as a consequence of the binding of the primary messengers to membrane receptors. (wikipedia.org)
  • coronary
  • This feature allows physicians to use adenosine to test for blockages in the coronary arteries, by exaggerating the difference between the normal and abnormal segments. (wikipedia.org)
  • The administration of adenosine also reduces blood flow to coronary arteries past the occlusion. (wikipedia.org)
  • Other coronary arteries dilate when adenosine is administered while the segment past the occlusion is already maximally dilated. (wikipedia.org)
  • activate
  • Neuroblastoma x glioma hybrid NG108-15 cells endogenously express at least three receptors which activate adenylate cyclase via the intermediacy of the stimulatory G-protein, Gs. (biochemj.org)
  • NOP acting through Gαi/o pathways has also been shown to activate Phospholipase A2 (PLA2), thereby initiating Mitogen-activated protein kinase (MAPK) signaling cascades. (wikipedia.org)
  • inhibit
  • Drugs that inhibit ADENOSINE DEAMINASE activity. (nih.gov)
  • Antiplatelet drugs like clopidogrel and prasugrel irreversibly inhibit the ADP receptor P2Y12, leading to a decreased ADP-induced platelet aggregation. (wikipedia.org)
  • Drugs that inhibit the GPIIb/IIIa receptor, e.g. eptifibatide, can also reduce or eliminate the ADP-induced platelet response. (wikipedia.org)
  • affinity
  • However, these analogues also possess good A1 receptor affinity resulting in low A2 selectivity. (unicam.it)
  • The presence of an a-quaternary carbon such as the 3-hydroxy-3,5-dimethyl-1-hexynyl (12) and the 3-hydroxy-3-phenyl-1-butynyl(1 5) derivatives markedly reduced the antiaggregatory potency without affecting the A2 affinity. (unicam.it)
  • prostanoid
  • Sustained exposure of the cells to agonists at the IP prostanoid receptor results in a substantial decrease in cellular levels of the alpha-subunit of Gs (Gs alpha) [McKenzie and Milligan (1990) J. Biol. (biochemj.org)
  • To examine whether this is a feature specific to the IP prostanoid receptor or is related to the level of expression of the individual receptors, NG108-15 cells were transfected with a construct containing a human beta 2-adrenoceptor cDNA under the control of the beta-actin promoter. (biochemj.org)
  • Cellular
  • These findings suggest that during pathological conditions such as inflammation or trauma, the significant amounts of cellular adenosine which are released may increase the production of NO by macrophage. (nus.edu.sg)
  • By contrast, equivalent treatments of the cells with agonists at either the A2 adenosine receptor or the secretin receptor have no measurable effect on cellular amounts of Gs alpha. (biochemj.org)
  • basal
  • A1 receptors are implicated in sleep promotion by inhibiting wake-promoting cholinergic neurons in the basal forebrain. (wikipedia.org)
  • neurotransmitter
  • Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, where they are received by neurotransmitter receptors on the target cells. (wikipedia.org)
  • A released neurotransmitter is typically available in the synaptic cleft for a short time before it is metabolized by enzymes, pulled back into the presynaptic neuron through reuptake, or bound to a postsynaptic receptor. (wikipedia.org)
  • Nevertheless, short-term exposure of the receptor to a neurotransmitter is typically sufficient for causing a postsynaptic response by way of synaptic transmission. (wikipedia.org)
  • Drugs
  • The existence of receptor oligomers is a general phenomenon, whose discovery has superseded the prevailing paradigmatic concept of the function of receptors as plain monomers, and has far-reaching implications for the understanding of neurobiological diseases as well as for the development of drugs. (wikipedia.org)
  • The dose is often decreased in patients on dipyridamole (Persantine) and diazepam (Valium) because adenosine potentiates the effects of these drugs. (wikipedia.org)
  • Heteromers
  • The actions of the A2A receptor are complicated by the fact that a variety of functional heteromers composed of a mixture of A2A subunits with subunits from other unrelated G-protein coupled receptors have been found in the brain, adding a further degree of complexity to the role of adenosine in modulation of neuronal activity. (wikipedia.org)
  • Receptor homomers consist of identical protomers, while heteromers consist of different protomers. (wikipedia.org)
  • mice
  • Cell counts, EBDA extravasation, as well as levels of proteins and inflammatory cytokines were decreased in adenosine-treated mice. (physiology.org)
  • Finally, when stimulated with cholinergic or cAMP agonists, cells from mice that lacked CFTR, as well as wild-type cells treated with a CFTR inhibitor, exhibited identical rates and magnitudes of shrinkage and Cl − efflux compared with control cells. (wiley.com)
  • activity
  • The hydrophobicity index (k') of the new nucleosides barely correlated with the binding data, whereas high k' values were associated with increased A2 vs A1 selectivity but with reduced activity in all unctional assays. (unicam.it)
  • Nitrite production and NOS activity in the RAW 264.7 cells were increased up to 2.5 fold after co-exposure of the cells to LPS and adenosine or its agonists, as compared to LPS alone. (nus.edu.sg)
  • Adenosine and its agonists had no effect on NOS activity when incubated alone with RAW 264.7 cells. (nus.edu.sg)
  • This receptors may have intrinsic catalytic activity or may be coupled to effector enzymes, or may also be associated to ionic channels. (wikipedia.org)
  • CamK Rapid changes in Ca2+ concentration, influenced by receptors such as those described above, regulate the activity of CaMKs. (wikipedia.org)
  • exposure
  • Acute ethanol exposure, a brief period of ethanol use, inhibits Ca2+ flow through NMDA receptors in the hippocampus, the brain structure particularly important in memory formation. (wikipedia.org)
  • muscarinic
  • Mass determination of β-adrenoceptors (1982) and muscarinic receptors (1983), supported the existence of homodimer or tetrameric complexes. (wikipedia.org)
  • Maggio and co-workers showed in 1993 the ability of the muscarinic M3 receptor and α2C-adrenoceptor to heterodimerize. (wikipedia.org)
  • thereby
  • In addition, A2A receptor can negatively regulate overreactive immune cells, thereby protecting tissues from collateral inflammatory damage. (wikipedia.org)